Based on the hypothesis that somatic mutagenesis plays an important role in both carcinogenesis and ageing, the research proposed in this grant will undertake the task of delineating the role of DNA repair mechanisms in mutagenesis in mammalian, including human, somatic cells in vitro. We propose to characterize the genetic and environmental influences on DNA repair, and hence, mutagenesis. We will measure induced mutation frequencies in human cells derived from patients genetically predisposed to cancer and/or ageing and compare them to mutation frequencies of normal individuals. Moreover, with the use of chemicals such as tumor promoters, hormones, inhibitors of DNA repair and cell division, we will characterize how various environmental agents can modify mutation frequencies when they modify DNA repair capacities. These studies will aid in the understanding of the molecular basis of mutagenesis, carcinogenesis and tumor promotion. BIBLIOGRAPHIC REFERENCES: J. E. Trosko, J. D. Yager, G. T. Bowden, and F. R. Butcher: "The effects of several croton oil constituents on two types of DNA repair and cyclic nucleotide levels in mammalian cells in vitro." Chem. Biol. Inter. 11:191-205 (1975). J. E. Trosko, and E. H. Y. Chu: "The role of DNA repair and somatic mutation in carcinogenesis." Advances in Cancer Research 21:391-425 (1975).